Manganese coordination compounds of mefenamic acid: In vitro screening and in silico prediction of biological activity.

The in vitro and in silico biological properties of two manganese complexes with the non-steroidal anti-inflammatory drug mefenamic acid (Hmef) in the presence or absence of salicylaldoxime (Η2sao), i.e. [Μn6(O)2(mef)2(sao)6(CH3OH)4] 1, and [Μn(mef)2(CH3OH)4] 2, respectively, are presented in the present contribution. More specifically, the in vitro biological activity of the complexes was investigated by studying their affinity to calf-thymus DNA (by diverse spectroscopic and physicochemical techniques) and their binding towards bovine (BSA) or human serum albumin (HSA) (by fluorescence emission spectroscopy). Molecular docking simulations on the crystal structures of HSA and DNA, exploring in silico the ability of the complexes to bind to these macromolecules, were also employed in order to explain the described in vitro activity of the compounds. Furthermore, in silico predictive tools have been employed to study the properties of the most active complex 2 to act as anticancer agent, in continuation of the previously reported cytotoxic activity. It is adopted in silico studies on a multitude of proteins involved in cancer growth, as well as prediction of drug-induced changes of gene expression profile, protein- and mRNA-based prediction results, prediction of sites of metabolism, quantitative prediction of antitarget interaction profiles etc.

In vitro and in silico study of the biological activity of manganese(III) inverse-[9-MC-3]-metallacrowns and manganese(II) complexes with the anti-inflammatory drugs diclofenac or indomethacin.

In the present contribution, the biological properties of four manganese complexes with the non-steroidal anti-inflammatory drugs sodium diclofenac (Nadicl) or indomethacin (Hindo) in the presence or absence of salicylaldoxime (Η2sao), i.e. [Μn6(O)2(dicl)2(sao)6(CH3OH)6] 1, [Μn6(O)2(indo)2(sao)6(H2O)4], 2, [Μn(dicl)2(CH3OH)4], 3, and [Μn(indo)2(CH3OH)4], 4 are presented. More specifically, the in vitro cytotoxic effects of the complexes were evaluated against three cancer cell lines (HeLa, MCF-7 and A549 cells) as well as their combinatory activity with the well-known chemotherapeutic drugs irinotecan, cisplatin, paclitaxel and 5-fluorouracil. The biological activity of the complexes was investigated in vitro by studying their affinity to calf-thymus DNA and their binding towards bovine or human serum albumin (HSA). Molecular docking simulations on the crystal structure of HSA and human estrogen receptor alpha (hERa) were employed in order to study in silico the ability of the studied complexes to bind to these proteins.

Interaction of zinc(II) with the non-steroidal anti-inflammatory drug niflumic acid.

The reaction of ZnCl2 with the non-steroidal anti-inflammatory drug niflumic acid (Hnif) resulted in the formation of complex [Zn(nif-O)2(MeOH)4], 1. When this reaction was performed in the presence of a N,N'-donor heterocyclic ligand such as 2,2'-bipyridine (bipy), 2,2'-bipyridylamine (bipyam), 1,10-phenanthroline (phen) and 2,2'-dipyridylketone oxime (Hpko), the complexes [Zn(nif-O,O')(bipy)Cl], 2, [Zn(nif-O)(nif-O,O')2(bipyam)], 3, [Zn(nif-O,O')2(phen)], 4 and [Zn(nif-O)2(Hpko-N,N')2], 5 were formed, respectively. The complexes were characterized by physicochemical and spectroscopic techniques and X-ray crystallography (for complexes 1-3). The complexes can scavenge 1,1-diphenyl-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals, may inhibit soybean lipoxygenase and are more active compounds than free Hnif. The interaction of the complexes with serum albumins was monitored by fluorescence emission spectroscopy and the corresponding binding constants were calculated. The affinity of the complexes with calf-thymus DNA was investigated by UV-vis spectroscopy, viscosity measurements and fluorescence emission spectroscopy for the competitive studies of the complexes with ethidium bromide revealing their interaction probably via intercalation.

Toward Multifunctional Materials Incorporating Stepladder Manganese(III) Inverse-[9-MC-3]-Metallacrowns and Anti-Inflammatory Drugs.

The interaction of Mn(ClO4)2·6H2O with salicylaldoxime (H2sao) in the presence of nonsteroidal anti-inflammatory drug (NSAID) sodium diclofenac (Nadicl) or indomethacin (Hindo) leads to the formation of the hexanuclear Mn(III) clusters [Mn6(O)2(dicl)2(sao)6(CH3OH)6] (1) and [Mn6(O)2(indo)2(sao)6(H2O)4] (2) both characterized as stepladder inverse-9-metallacrown-3 accommodating dicl- or indo- ligands, respectively. When the interaction of MnCl2·4H2O with Nadicl or Hindo is in the absence of H2sao, the mononuclear Mn(II) complexes [Mn(dicl)2(CH3OH)4] (3) and [Mn(indo)2(CH3OH)4] (4) were isolated. The complexes were characterized by physicochemical and spectroscopic techniques, and the structure of complexes 1 and 2 was characterized by X-ray crystallography. Magnetic measurements (dc and ac) were carried out in order to investigate the nature of magnetic interactions between the magnetic ions and the overall magnetic behavior of the complexes.

Zinc complexes of diflunisal: Synthesis, characterization, structure, antioxidant activity, and in vitro and in silico study of the interaction with DNA and albumins.

From the reaction of ZnCl2 with the non-steroidal anti-inflammatory drug diflunisal (Hdifl), complex [Zn(difl-O)2(MeOH)4], 1 was formed, while in the presence of a N,N'-donor heterocyclic ligand 2,2'-bipyridylamine (bipyam), 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen) and 2,2'-dipyridylketone oxime (Hpko), the complexes [Zn(difl-O,O')2(bipyam)], 2, [Zn(difl-O,O')2(bipy)], 3, [Zn(difl-O,O')2(phen)], 4 and [Zn(difl-O)2(Hpko)2], 5 were isolated, respectively. The complexes were characterized by physicochemical and spectroscopic techniques and the crystal structures of complexes 2, 3 and 5 were determined by X-ray crystallography. The ability of the complexes to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals and to inhibit soybean lipoxygenase was studied and the complexes were more active than free Hdifl. The interaction of the complexes with serum albumins was monitored by fluorescence emission spectroscopy and the corresponding binding constants were calculated. UV-vis spectroscopy, viscosity measurements and fluorescence emission spectroscopy for the competitive studies of the complexes with ethidium bromide were employed to investigate the interaction of the complexes with calf-thymus DNA and revealed intercalation as the most possible DNA-binding mode. Computational techniques were used to identify possible binding sites of albumins and DNA, and determine the druggability of human and bovine serum albumins with the five novel complexes. The majority of the complexes are stronger binders than the free Hdifl. This is the first study incorporating experimental and computational results to explore the binding activity of metal-NSAID complexes with DNA and serum albumins, suggesting their application as potential metallodrugs.

Zinc complexes of flufenamic acid: Characterization and biological evaluation.

The reaction of ZnCl2 with the non-steroidal anti-inflammatory drug flufenamic acid (Hfluf) led to the formation of complex [Zn(fluf-O)2(MeOH)4], 1. When the reaction takes places in the presence of a N,N'-donor heterocyclic ligand such as 2.2'-bipyridylamine (bipyam), 2.2'-bipyridine (bipy), 1.10-phenanthroline (phen) and 2.2'-dipyridylketone oxime (Hpko), the complexes [Zn(fluf)2(bipyam)], 2, [Zn(fluf)2(bipy)], 3, [Zn(fluf)(phen)2(H2O)](fluf)·0.2MeOH, 4·0.2MeOH and [Zn(fluf)2(Hpko)2], 5 were isolated, respectively. The complexes were characterized by physicochemical and spectroscopic techniques and the crystal structures of complexes 2 and 4 were determined by X-ray crystallography. The ability of the complexes to scavenge 1.1-diphenyl-picrylhydrazyl, 2.2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals and to inhibit soybean lipoxygenase was evaluated; the complexes were more active than free Hfluf. The interaction of the complexes with serum albumins was investigated by fluorescence emission spectroscopy and the corresponding binding constants were calculated. UV-vis spectroscopy, viscosity measurements and fluorescence emission spectroscopy for the competitive studies of the complexes with ethidium bromide were the techniques employed to monitor the interaction of the complexes with calf-thymus DNA and revealed intercalation as the most possible mode of binding.

Cobalt(II) complexes with non-steroidal anti-inflammatory drugs and α-diimines.

Cobalt(II) complexes with a series of non-steroidal anti-inflammatory drugs (diflunisal, flufenamic acid, mefenamic acid and niflumic acid) in the presence of nitrogen-(2,2'-bipyridylamine, 2,2'-bipyridine, 1,10-phenanthroline) and/or oxygen-donor ligands (methanol) have been synthesized and characterized with physicochemical and spectroscopic techniques. The deprotonated NSAID ligands are coordinated to Co(II) ion through their carboxylato groups in diverse binding modes. The crystal structures of complexes [Co(diflunisal-O)2(methanol)4], [Co(niflumato-O)2(methanol)4], [Co(flufenamato-O,O')2(2,2'-bipyridylamine)], [Co(mefenamato-O,O')2(2,2'-bipyridylamine)] and [Co3(flufenamato-O,O')4(flufenamato-O,O,O')2(2,2'-bipyridine)2] have been determined by X-ray crystallography. The interaction of the complexes with serum albumins was studied by fluorescence emission spectroscopy and the albumin-binding constants were determined. The ability of the complexes to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals was investigated and the complexes were more active than the corresponding free drugs. Spectroscopic (UV and fluorescence), electrochemical (cyclic voltammetry) and physicochemical (viscosity measurements) techniques were employed in order to study the binding mode of the complexes to calf-thymus (CT) DNA and to calculate the corresponding binding constants; for all complexes, intercalation was suggested as the most possible DNA-binding mode.

Copper(II) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid: Structure and biological features.

Copper(II) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid (Htolf) with the oxygen-donor ligands methanol (MeOH) or N,N-dimethylformamide (DMF) and/or the nitrogen-donor heterocyclic ligands 2,2'-bipyridine (bipy), 2,2'-bipyridylamine (bipyam), 1,10-phenanthroline (phen) or pyridine (py) were synthesized and characterized. The crystal structures of five novel complexes were determined by X-ray crystallography where tolfenamic acid is deprotonated being in different binding modes. Equimolar quantities of CuCl2, tolf(-1) and bipy led to the formation of [Cu(tolf-O,O')(bipy)Cl] (1), while with a 1:2 Cu(II):tolf ratio, complexes [Cu(tolf-O,O')2(bipy)] (2), [Cu(tolf-O,O')2(bipyam)] · 0.5MeOH (3 0.5MeOH), [Cu(tolf-O,O')(tolf-O)(phen)(MeOH)] (4) and [Cu(tolf-O)2(py)2(MeOH)2] (5) were isolated. The interaction of the complexes with serum albumin proteins was studied by fluorescence spectroscopy with the determined binding constant bearing relative high values. The scavenging ability of the complexes towards 1,1-diphenyl-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals was investigated and the in vitro inhibitory activity against soybean lipoxygenase was evaluated and complexes 4 and 5 were the more active compounds among those tested. Spectroscopic (UV), electrochemical (cyclic voltammetry) and physicochemical (viscosity measurements) techniques were employed in order to study the binding mode and strength of the complexes to calf-thymus (CT) DNA suggesting intercalation as the most possible mode of binding. Competitive studies with ethidium bromide (EB) revealed the ability of the complexes to displace the DNA-bound EB. The biological properties of complexes 1-5 were evaluated in regard to previously reported complex [Cu2(tolf-O,O')4(DMF)2] (6).

Structure and biological perspectives of Cu(II)-indomethacin complexes.

The copper(II) complexes with the non-steroidal anti-inflammatory drug indomethacin (Hindo) in the presence of the nitrogen-donor heterocyclic ligands 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen) or 2,2'-bipyridylamine (bipyam) have been synthesized and characterized. The crystal structures of [Cu(indo)2(bipy)]∙1.5MeOH∙0.5H2O and [Cu(indo)2(phen)] ∙1.85MeOH∙0.15H2O have been determined by X-ray crystallography. All compounds have been tested for their antioxidant and free radical scavenging activity as well as for their in vitro inhibitory activity against soybean lipoxygenase showing significant activity with the previously reported complex [Cu2(indo)4(H2O)2] being the most active. The complexes exhibit good binding affinity to human or bovine serum albumin protein with high binding constant values. UV study of the interaction of the complexes with calf-thymus (CT) DNA has shown that the complexes can bind to CT DNA with [Cu(indo)2(bipyam)] showing the highest binding constant to CT DNA (Kb=1.56(±0.19)×10(6)M(-1)). The complexes can bind to CT DNA via intercalation as concluded by cyclic voltammetry, DNA viscosity measurements and competitive studies with ethidium bromide (EB) which revealed the ability of the complexes to displace the DNA-bound EB.

Antioxidant activity and interaction with DNA and albumins of zinc-tolfenamato complexes. Crystal structure of [Zn(tolfenamato)2(2,2'-dipyridylketoneoxime)2].

The zinc(II) complex of the non-steroidal anti-inflammatory drug tolfenamic acid (=Htolf) in the presence of 2,2'-dipyridylketone oxime (=Hpko) as a N,N'-donor heterocyclic ligand, [Zn(tolf-O)2(Hpko-N,N')2]·MeOH (=1·MeOH), has been synthesized and characterized by physicochemical techniques including X-ray crystallography. The complex exhibits good binding affinity to human or bovine serum albumin with high binding constant values. Complex 1 and previously reported Zn-tolfenamato complexes were tested for their free radical scavenging activity and in vitro inhibitory activity against soybean lipoxygenase and exhibited significant activity with [Zn(tolf)2(1,10-phenantroline)] being the most active compound. The complexes interact with calf-thymus (CT) DNA via intercalation, and can displace the DNA-bound ethidium bromide with 1 exhibiting the highest binding constant to CT DNA.

Antioxidant capacity and DNA-interaction studies of zinc complexes with a non-steroidal anti-inflammatory drug, mefenamic acid.

Zinc(II) complexes of a non-steroidal anti-inflammatory drug, mefenamic acid(=Hmef) in the absence or presence of the nitrogen donor heterocyclic ligands 2,2'-bipyridine(=bipy), 2,2'-bipyridylamine(=bipyam), 2,2'-dipyridylketone oxime(=Hpko) or 1,10-phenanthroline(=phen) have been synthesized and characterized. The crystal structures of [Zn(mef-O,O')2(bipy)], 2, [Zn(mef-O)2(Hpko-N,N')2]·EtOH, 4 and [Zn(mef-O)(mef-O,O')(phen)(H2O)], 5, have been determined by X-ray crystallography showing distinct binding modes of mefenamato carboxylato group, bidentate in 2, monodentate in 4 or both in 5. Interaction studies of the complexes with calf-thymus DNA (CT DNA) have shown that complexes can bind to CT DNA with [Zn(mef-O)2(Hpko)2] exhibiting the highest binding constant to CT DNA (Kb = 1.93(±0.04) × 10(7) M(-1)). The complexes can bind to CT DNA via intercalation as concluded by DNA solution viscosity measurements. Competitive studies with ethidium bromide (EB) have shown that the complexes can displace the DNA-bound EB. The complexes exhibit good binding affinity to serum albumin proteins with [Zn(mef-O)2(H2O)4], 1 exhibiting the highest quenching ability (kq = 1.46 × 10(15) M(-1) s(-1) for human and 5.55 × 10(15) M(-1) s(-1) for bovine serum albumin). All compounds have been tested for their antioxidant and free radical scavenging activity as well as for their in vitro inhibitory activity against soybean lipoxygenase. The scavenging activity is low to moderate against 1,1-diphenyl-picrylhydrazyl (DPPH) radicals and high against hydroxyl and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(+·)) radicals, with [Zn(mef-O)2(H2O)4], 1 (ABTS%, 0.1 mM: 94.75(±1.06)%; (·)OH%, 0.1mM: 96.69(±0.27)%; LOX: IC50 = 27.34(±0.90) µM) exhibiting the highest scavenging activity of the ABTS radical cation among the complexes. Additionally, the complexes exhibit higher scavenging and LOX inhibitory activity than free mefenamic acid (ABTS%, 0.1 mM: 66.32(±0.38)%; (·)OH%, 0.1 mM: 92.51(±0.44)%; LOX: IC50 = 48.52(±0.88) µM).

Quinolones and non-steroidal anti-inflammatory drugs interacting with copper(II), nickel(II), cobalt(II) and zinc(II): structural features, biological evaluation and perspectives.

The structural features of copper(II), nickel(II), cobalt(II) and zinc(II) complexes with the antimicrobial drugs quinolones and non-steroidal anti-inflammatory drugs (NSAIDs) as ligands are discussed. The binding properties of these complexes to biomolecules (calf-thymus DNA, bovine or human serum albumin) are presented and evaluated. The biological activity (antimicrobial, antioxidant and antiproliferative) of selected complexes is investigated. Further perspectives concerning the synthesis and the biological activity of novel complexes with quinolones or NSAIDs attractive to synthetic chemists, biochemists and/or biologists are presented.

First- and second-generation quinolone antibacterial drugs interacting with zinc(II): structure and biological perspectives.

Interaction of equimolar quantities of ZnCl2 with the quinolone antibacterial drugs flumequine (Hflmq), oxolinic acid (Hoxo) or enrofloxacin (Herx) and the N,N'-donor heterocyclic ligands 1,10-phenanthroline (phen) or 2,2'-bipyridine (bipy) results in the formation of 1:1 drug to metal complexes with the general formula [Zn(quinolone)(N,N'-donor)Cl], while excess of the quinolone leads to 1:2 metal to drug [Zn(quinolone)2(N,N'-donor)] complexes. In all complexes, the deprotonated bidentate quinolonato ligands are coordinated to zinc ion through the pyridone oxygen and a carboxylato oxygen. The crystal structures of [Zn(oxo)(phen)Cl], [Zn(flmq)(phen)Cl] and [Zn(flmq)2(phen)] have been determined by X-ray crystallography. All complexes exhibit good binding propensity to human or bovine serum albumin protein showing relatively high binding constant values. Interaction of the complexes with calf-thymus (CT) DNA, studied by UV spectroscopy, has shown that they bind to CT DNA, while [Zn(flmq)(phen)Cl] and [Zn(flmq)2(phen)] complexes exhibit the highest binding constants to CT DNA. Competitive study with ethidium bromide (EB) has shown that all complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. Intercalative binding mode is proposed for the interaction of the complexes with CT DNA and has also been verified by DNA solution viscosity measurements. DNA electrophoretic mobility experiments suggest that all complexes bind to linearized pDNA and supercoiled pDNA by intercalative manner resulting in catenanes formation as well as in double-stranded cleavage reflecting (or ending) in the formation of linear DNA. The complexes exhibit significant antimicrobial activity tested on five different microorganisms.

A [24-MC-6] zinc metallacoronate with a nonsteroidal antiinflammatory drug as the constructing ligand.

The interaction of ZnCl(2) with 2-dipyridylketonoxime (=Hpko) and flufenamic acid (=Hfluf) in a basic methanolic solution leads to the formation of a hexanuclear 24-membered metallacoronate, [Zn(6)(OH)(2)(pko)(4)(fluf)(6)] (1), with a [Zn-O-C-O] repeat unit and a nonsteroidal antiinflammatory drug as the constructing ligand. Compound 1 retains its structure in a dimethyl sulfoxide solution, as shown by (1)H NMR spectroscopy and molar conductance.

Copper(II) complexes with antimicrobial drug flumequine: structure and biological evaluation.

The copper(II) complexes with the first-generation quinolone antibacterial agent flumequine(Hflmq) in the presence or absence of the nitrogen donor heterocyclic ligands 2,2'-bipyridylamine(bipyam), 2,2'-bipyridine(bipy), 1,10-phenanthroline(phen) or pyridine(py) have been synthesized and characterized. Flumequine acts as bidentate ligand coordinated to Cu(II) atom through the pyridone oxygen and a carboxylato oxygen. The crystal structures of the complexes [Cu(flmq)(bipyam)Cl], [Cu(flmq)(bipy)Cl] and [Cu(flmq)(phen)Cl] have been determined by X-ray crystallography revealing a distorted square pyramidal geometry for Cu(II) atom. The interaction of the complexes with bovine or human serum albumin proteins has been studied by fluorescence spectroscopy revealing their good binding propensity to the proteins with relatively high binding constant values. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they bind to CT DNA and [Cu(flmq)(2)(py)(2)] exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes have shown that in the presence of CT DNA the complexes can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide(EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB.

Structural features of mono- and tri-nuclear Zn(II) complexes with a non-steroidal anti-inflammatory drug as ligand.

The interaction of Zn(II) with the non-steroidal anti-inflammatory drug tolfenamic acid leads to the formation of the structurally characterized trinuclear [Zn(3)(tolfenamato)(6)(CH(3)OH)(2)] complex. In the presence of the N,N'-donor heterocyclic ligands 1,10-phenanthroline and 2,2'-bipyridine at a range of ratios, the mononuclear Zn complexes of the general formulae [Zn(tolfenamato)(N,N'-donor)Cl] and [Zn(tolfenamato)(2)(N,N'-donor)] have been isolated and structurally characterized by X-ray crystallography. The deprotonated tolfenamato ligands are coordinated to the Zn(II) ion through carboxylato oxygen atoms. Tolfenamic acid and its complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.

Biological evaluation of cobalt(II) complexes with non-steroidal anti-inflammatory drug naproxen.

Cobalt(II) complexes with the non-steroidal anti-inflammatory drug naproxen in the presence or absence of nitrogen-donor heterocyclic ligands (pyridine, 2,2'-bipyridine or 1,10-phenanthroline) have been synthesized and characterized with physicochemical and spectroscopic techniques. The deprotonated naproxen acts as monodentate ligand coordinated to Co(II) ion through a carboxylato oxygen. The crystal structure of [bis(aqua)bis(naproxenato)bis(pyridine)cobalt(II)], 2 has been determined by X-ray crystallography. The EPR spectrum of complex 2 in frozen solution reveals that it retains its structure. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA and [(2,2'-bipyridine)bis(methanol)bis(naproxenato)cobalt(II)] exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes recorded in DMSO solution and in the presence of CT DNA in 1/2 DMSO/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that they can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. Naproxen and its cobalt(II) complexes exhibit good binding propensity to human or bovine serum albumin proteins having relatively high binding constant values. The antioxidant activity of the compounds has been evaluated indicating their high scavenging activity against hydroxyl free radicals and superoxide radicals.

Cobalt(II) complexes with non-steroidal anti-inflammatory drug tolfenamic acid: Structure and biological evaluation.

Cobalt(II) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid in the presence or absence of nitrogen-donor heterocyclic ligands (2,2'-bipyridine, 1,10-phenanthroline, 2,2'-bipyridylamine or pyridine) have been synthesized and characterized with physicochemical and spectroscopic techniques. The deprotonated tolfenamato ligands are coordinated to Co(II) ion through carboxylato oxygen atoms. The crystal structures of complexes [bis(2,2'-bipyridine) bis(methanol)bis(tolfenamato)cobalt(II)] 2 and [bis(2,2'-bipyridylamine)bis(tolfenamato)cobalt(II)] 4 have been determined by X-ray crystallography. UV studies of the interaction of the complexes with calf-thymus DNA (CT DNA) have shown that the complexes can bind to CT DNA and [bis(methanol)(1,10-phenanthroline)bis(tolfenamato)cobalt(II)] exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes recorded in DMSO solution and in the presence of CT DNA in 1/2 DMSO/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that they can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. Tolfenamic acid and its cobalt(II) complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.

Non-steroidal anti-inflammatory drug diflunisal interacting with Cu(II). Structure and biological features.

Copper(II) complexes with the non-steroidal anti-inflammatory drug diflunisal in the presence of N,N-dimethylformamide or nitrogen donor heterocyclic ligands (pyridine, 1,10-phenanthroline, 2,2'-bipyridine or 2,2'-bipyridylamine) have been synthesized and characterized. The deprotonated diflunisal ligands are coordinated to Cu(II) ion through carboxylato oxygen atoms. The crystal structures of [tetrakis(diflunisal)bis(N,N-dimethylformamide)dicopper(II)] 1 and [bis(diflunisal)bis(pyridine)copper(II)], 2 have been determined by X-ray crystallography and are the first reported crystal structures of diflunisal complexes. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) suggests binding of the complexes to CT DNA with the dinuclear [tetrakis(diflunisal)bis(N,N-dimethylformamide)dicopper(II)] compound exhibiting the highest binding constant, K(b). Intercalative binding mode may also be concluded using cyclic voltammetry and solution viscosity measurements of the complexes in the presence of CT DNA. Competitive studies with ethidium bromide (EB) indicate that the complexes can displace the DNA-bound EB suggesting competition with EB. Diflunisal and its complexes exhibit good binding propensity to human or bovine serum albumin protein showing relatively high binding constant values.

Non-steroidal antiinflammatory drug-copper(II) complexes: structure and biological perspectives.

Copper(II) complexes with the non-steroidal antiinflammatory drug mefenamic acid in the presence of aqua or nitrogen donor heterocyclic ligands (2,2'-bipyridine, 1,10-phenanthroline, 2,2'-bipyridylamine or pyridine) have been synthesized and characterized. The crystal structures of [(2,2'-bipyridine)bis(mefenamato)copper(II)], 2, [(2,2'-bipyridylamine)bis(mefenamato)copper(II)], 4, and [bis(pyridine)bis(methanol)bis(mefenamato)copper(II)], 5, have been determined by X-ray crystallography. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA and [bis(aqua)tetrakis(mefenamato)dicopper(II)] exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes in the presence of CT DNA solution have shown that the complexes can bind to CT DNA by the intercalative binding mode verified also by DNA solution viscosity measurements. Competitive studies with ethidium bromide (EB) indicate that the complexes can displace the DNA-bound EB suggesting strong competition with EB. Mefenamic acid and its complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. All the compounds have been tested for their antioxidant and free radical scavenging activity as well as for their in vitro inhibitory activity against soybean lipoxygenase showing significant activity.